Medication of Diseases News - Part 7

This was a retrospective study that compared total health-care costs and rates of adverse clinical outcomes in two groups of at-risk patients receiving long-term warfarin therapy who received bridge therapy in the perioperative period with UH or LMWH for an elective surgical procedure during the temporary cessation of warfarin therapy. Costs were examined for the bridging episode, which was defined as the period from 10 days before the procedure through 30 days after the procedure. Adverse clinical events that occurred following the procedure were identified from day 1 through day 30 postprocedure. The study protocol was reviewed by the Lovelace Institutional Review Board and was given exempt status.

Pharmacoeconomic analyses support the cost-effectiveness, cost savings, or economic dominance of the use of LMWH over that of UH for the inpatient treatment of venous thrombosis, the outpatient management of uncomplicated deep vein thrombosis, thromboprophylaxis in orthopedic surgery, and the management of acute coronary syn-dromes. Most of these analyses support the notion that the cost savings from LMWH therapy stem from shifting costs from the inpatient to the less expensive outpatient environment or from the greater effectiveness of treatment.
To date, there have been no cost evaluations comparing the use of LMWH to that of UH in the perioperative period for the patient receiving longterm OAC therapy requiring the temporary interruption of therapy to undergo an elective surgical procedure. Therefore, we conducted a retrospective study, the primary objective of which was to compare the health-care costs of patients who were treated on a mostly outpatient basis with the LMWH enoxapa-rin to the health-care costs of patients who were treated with IV UH as hospital inpatients.

The optimal perioperative management of at-risk patients on long-term oral anticoagulant (OAC) therapy remains problematic. Although most patients can safely undergo procedures such as diagnostic endoscopy, cataract surgery, arthrocentesis, and oral surgery/dental extractions without an alteration of OAC therapy in the periprocedural period, the conventional care for the perioperative management of high-risk patients requiring continuous anticoagulant therapy involves the use of IV unfractionated heparin (UH) as “bridge therapy” during periods of subtherapeutic levels of oral anticoagulation. Consensus guidelines for the management of anticoagulation therapy in the perioperative period, especially with the use of IV or subcutaneous UH, are based on expert opinion or mathematical modeling. In the preoperative period, this is accomplished in conjunction with the cessation of OAC therapy until a safe target international normalized ratio (INR) is reached to minimize the bleeding risk associated with the procedure (usually an INR of < 1.5). In the postoperative period, therapy with IV or subcutaneous UH is resumed along with OAC therapy until a previously defined therapeutic INR is reached (usually 2.0).

Feeding alveolar macrophages with E coli bacteria did not result in a significant difference of the phagocytic activity of alveolar macrophages from HIV-1 seropositive subjects, when compared to normal, seronegative control subjects. Moreover, there was no correlation between the phagocytic activity and parameters of infection with HIV-1 eg, the peripheral CD4 positive lymphocyte count or the viral load of the patients. However, we found that macrophages from HIV-positive smokers had a significantly lower phagocytic activity compared to HIV-positive nonsmokers. This was true for both model targets chosen, E coli and IgG-opsonized SRBCs.

Opsonized phagocytosis is critical to lung defense, We have previously noted that individuals with HIV-1 infection are not deficient in the potential to opsonize pathogens based on the IgG levels in lung lavage fluid. We therefore tested a second set of individuals with HIV-1 infection (Table 4) and control subjects for the ability of their lung macrophages to phagocytose opsonized SRBCs. Using IgG-opso-nized SRBCs as a target, we again confirmed no detectable difference in phagocytic index between HIV-positive individuals (n = 5) and normal control subjects (n = 5) [Fig 3] or when expressed as numbers of SRBCs ingested per phagocytic cell over time (Table 5). However, when the data were reanalyzed by smoking status alone, smokers had a statistically significant depression in their phagocytic index at all time points, p < 0.05 (at 10 min, 135 ± 13 vs 78 ± 16; at 20 min, 305 ± 27 vs 132 ± 33; at 30 min, 437 ± 34 vs 233 ± 42; and at 60 min, 644 ± 56 vs 401 ± 80 for nonsmokers vs smokers, respectively) [Fig 4, top, А]. Subset analysis (Fig 4, bottom, B) once again suggested that the combination of HIV and smoking had a more profound effect on phagocytosis than either HIV or smoking. http://www.pilocarpine-eyedrops.com/

Statistics were performed using SigmaStat statistical software (SPSS; Chicago, IL). Comparisons of groups for statistical difference were done using the Student t test after passing the normality and the equal variance test. In cases where the equal variance test failed, the Mann Whitney rank-sum test was applied. Simple linear regression analysis was done to describe the dependent variable as a function of possible independent variables.

Fluorescein-labeled E coli bacteria were purchased from Molecular Probes Inc. (Eugene, OR), added to alveolar macrophages in a ratio of 106 bacteria/105 macrophages in suspension in RPMI 1640. At time zero, the cells were pelleted by low-speed centrifugation (200g) to increase contact between bacteria and phagocytes. The samples were prepared in duplicate and incubated for different time intervals (0 min, 30 min, 1h) at 37°C before fixation in 1% paraformaldehyde. The phagocytosis of fluorescein-labeled E coli was quantified using computer-based image analysis; 3 μL of trypan blue stain (Gibco BRL; Grand Island, NY) was added to 10 μL of the cell sample to quench any free floating and adherent bacteria. The cell suspension was then placed on a microscope slide with a cover slip. Bright-field photographs and fluorescent photographs were taken and analyzed using Image Pro-plus computer program (Media Cybernetics; Silver Spring, MD). The software estimated the ratio of bacteria phagocytosed per cell based on the amount of green fluorescence per cell normalized to the amount of fluorescence per one bacterium. www.xalatan-eye-drops.com

Study Subjects
Over a period of 1 year, HIV-seronegative and asymptomatic HIV-seropositive individuals without evidence for active pulmonary disease were prospectively recruited. Demographic characteristics recorded for all participants included age, sex, and smoking status. Additionally, the peripheral CD4+ T-lymphocyte counts and viral load were determined for the HIV-seropositive individuals.
The capacity to phagocytose E coli bacteria was studied in nine HIV-1-seronegative (control group) and eight HIV-1-seropositive individuals (HIV-1 group). The demographic characteristics of the individual study groups are provided in Table 1. The cell differential of both groups showed no significant differences in the total cell count and the relative composition of the individual cell types (Table 2). Bacteria phagoytosed permacrophase in subjects over time are presented in Table 3. To study the phagocytosis of opsonized SRBCs, 10 HIV-1-seropositive individuals classified as 4 smokers and 6 nonsmokers were recruited. Demographic characteristics are shown in Table 4.

Alveolar macrophages reside in the alveolar space and account for > 85% of the total cells in this compartment. They play an important role in the pulmonary defense against microorganisms and are strategically placed to protect the large surface of the respiratory epithelium. Alveolar macrophages can induce specific immune responses, including antigen presentation to T cells, and contribute significantly to the innate immunity of the lung. Besides their secretory functions, alveolar macrophages are highly phagocytic cells with the capability to engulf and digest microorganisms such as viruses and bacteria or other particles, eg, RBCs, apoptotic bodies, and cellular debris.

The lung materials examined in the present study were usually fixed at their maximum expiratory point at death. However, chest physiotherapy is generally performed in the tidal volume range. How much difference in the bronchial courses and branching angles would there be for the fixed cadaveric lungs? Can some of the extreme variation in branching angles be attributed to the maximum expiratory point at death? Although further intensive studies might be necessary to resolve these questions, using three-dimensionally reconstructed images obtained from high-resolution CT for three pairs of healthy lungs of the present authors (N.T., G.M., A.I.), we investigated the difference in branching angles between the tidal volume range and forced expiratory point. The results were summarized as follows: (1) effectiveness for the segmental drainage seemed to be almost consistent because the changes in branching angles of all segmental bronchi were limited to ± 5° except for B and B with + 10 to + 15° (thus, they became more effective); (2) the changes in subsegmental bronchial angles ranged from 26 to + 38° (mean, + 5.2°) in B, B1 + 2, B, and B; and (3) changes in branching angles of another subsegmental bronchi, such as in the middle and lower lobes, were limited to ± 10° and provided no negative influence on the effectiveness category.